Comparative efficacy & safety of buparlisib plus fulvestrant, fulvestrant plus dalpiciclib, and ribociclib plus letrozole for postmenopausal, hormone receptor-positive, and HER2-negative breast cancer

Abstract Objectives: This study aimed to compare progression-free survival, overall survival, clinical benefits, and adverse effects in postmenopausal women with hormone receptor-positive and HER2-negative breast cancer who received buparlisib plus fulvestrant against those of women who received dalpiciclib plus fulvestrant, considering ribociclib plus letrozole treatment as the reference standard. Methods: Women received buparlisib plus fulvestrant (BF cohort, n = 108), dalpiciclib plus fulvestrant (DF cohort, n = 132), or ribociclib plus letrozole (RL cohort, n = 150) until unacceptable toxicity was observed. Results: A total of 117 (89 %), 80 (74 %), and 84 (56 %) women in the BF, DF, and RL cohorts, respectively, had clinical benefits. After treatment, the clinical benefits for women and after 42 months of follow-up progression-free survival and overall survival were higher in the DF cohort than in the BF and RL cohorts (p < 0.05 for all). Neutropenia, vomiting, constipation, nausea, diarrhea, and anorexia were reported higher in women of the DF and BF cohorts than in women of the RL cohort. Leukopenia and increased levels of alanine aminotransferase and aspartate aminotransferase were reported to be higher in women in the RL cohort than in women in the DF and BF cohorts. Depression, anxiety, and increased levels of alanine aminotransferase and aspartate aminotransferase were reported to be higher in women in the BF cohort than in women in the DF and RL cohorts. Conclusions: Dalpiciclib plus fulvestrant is effective and comparatively safe in postmenopausal women with hormone receptor-positive and HER2-negative breast cancers. Dalpiciclib, buparlisib, fulvestrant, and ribociclib cause neutropenia, severe depression, adverse gastroenterological effects, and adverse hepatological effects, respectively.

Effects of metformin hydrochloride tablets on clinical efficacy and number of dominant follicles in polycystic ovary syndrome / 药学实践杂志

Objective To explore the effect of metformin hydrochloride tablets on the clinical efficacy, number of dominant follicles and ovarian volume of polycystic ovary syndrome. Methods 150 patients diagnosed with polycystic ovary syndrome who were diagnosed and treated in our hospital from January 2019 to March 2021 were selected .The patients were divided into observation group and control group by random number table. The control group was treated with letrozole + gonadotropin, and the observation group was treated with letrozole + gonadotropin + hydrochloric acid + Metformin tablets. The clinical efficacy, endometrial thickness, number of high-quality follicles, sex hormone levels, blood lipid levels, and adverse reactions were compared between the two groups. Results ① The effective rate of treatment in the observation group was 90.67%, which was significantly higher than that in the control group, 78.67% (P<0.05). ② After treatment, the endometrial thickness of the observation group was lower than that of the control group, and the number of high-quality follicles was more than that of the control group(P<0.05). ③ After treatment, the levels of Luteinizing Hormone-LH, Follicle Stimulating Hormone-FSH and Testosterone (T) in the observation group were lower than those in the control group (P<0.05). ④ After treatment, the total cholesterol (TC) and triglyceride (TG) in the observation group were lower than those in the control group (P<0.05). ⑤ The incidence of adverse reactions in the observation group was 8.00%, which was significantly lower than 20.00% in the control group (P<0.05). Conclusion Letrozole + gonadotropin + metformin hydrochloride tablets could significantly improve the sex hormone and blood lipid levels in patients with polycystic ovary syndrome, relieve the symptoms of the patients, and improve their uterine condition, which had a good clinical effect.

AN OBSERVATIONAL ANALYSIS OF CLINICAL PROFILE ASSOCIATED WITH OVULATION INDUCTION USING LETROZOLE AMONG INFERTILE WOMEN WITH POLYCYSTIC OVARIAN SYNDROME

Background- Polycystic ovary syndrome (PCOS) is major endocrine and metabolic disease in reproductive women. As per latest procedures, letrozole should be taken as the first-line pharmacological treatment for infertile women with PCOS. This study was planned to study the role of clinical profile in ovulation induction after letrozole therapy among infertile women with polycystic ovarian syndrome. This was a prospective analytical observational st Methods- udy carried out at the IVF centre, SMS Medical College, Jaipur. The present study enrolled 100 patients attending the IVF centre for fertility treatment who were diagnosed with PCOS as per Rotterdam criteria. Anthropometric measurements like Body mass index (BMI calculated as weight in kilograms divided by square of height in meters) and waist circumference (the smallest circumference at the level of umbilicus) was taken. A comprehensive physical examination of all patients was done to note signs of clinical hyperandrogenism like acne, alopecia, and hirsutism. Treatment response was defined as ovulation in response to letrozole in doses from 2.5 mg to 7.5 mg. In this study, women from 20 to 25 years of age w Results- ith shorter duration of infertility, lower BMI, lower waist circumference, absence of hirsutism, or mild hirsutism on clinical examination showed better response to Letrozole. ConclusionLetrozole can be considered a suitable ovulation induction agent in infertile PCOS patients with lower BMI, lower waist circumference, and absence of hirsutism. A predictive ovulation score can be developed from basic clinical parameters. Identification of various factors affecting response to letrozole may help the clinician to individualize ovulation induction protocols in PCOS women.

Investigation of teratogenic effects of letrozole on fetal bone development / Investigación de los efectos teratogénicos de letrozol en el desarrollo óseo fetal

SUMMARY: Letrozole is mainly used for the treatment of unexplained infertility, breast cancer and polycystic ovarian syndrome, with secondary use in ovarian stimulation. In cases of unexpected or unknown pregnancy during the use of letrozole, letrozole may cause a teratogenic effect on the fetus. In this reason, in this study, we aimed to determine the effect of letrozole on fetal bone development. In this study, 32 pregnant Wistar albino rats were used. The rats were divided into four groups: Control (saline) and high; 0.3 mg/kg, medium; 0.03 mg/kg, low; 0.003 mg/ kg letrozole. Saline and letrozole were administered in 100 mL solutions by intraperitonaly from day 11 to day 15 of pregnancy. The skeletal system development of fetuses was examined with double skeletal staining, immunohistochemical staining methods and mineral density scanning electron microscopy. A total of 100 fetuses from female rats, 25 in each group, were included in the study. As a result of that, ossification rates were observed to decrease depending on the dose of letrozole in the forelimb limb (scapula, humerus, radius, ulna) and hindlimb (femur, tibia, fibula) limb bones. As a result of the statistical analysis, a statistically significant decrease was found in the ossification rates of all bones between the control group and low, medium, high letrozole groups (p<0.001). Exposure to letrozole during pregnancy adversely affected ossification and bone growth. However, the teratogenic effects of letrozole are unclear. Therefore, it needs to be investigated more extensively.

RESUMEN: Letrozol se usa principalmente para el tratamiento de la infertilidad inexplicable, el cáncer de mama y el síndrome de ovario poliquístico, con estimulación ovárica de uso secundario. En casos de embarazo inesperado o desconocido durante el uso de letrozol, puede causar un efecto teratogénico en el feto. Por esta razón, en este estudio, nuestro objetivo fue determinar el efecto de letrozol en el desarrollo óseo fetal. Se utilizaron 32 ratas albinas Wistar preñadas las cuales se distribuyeron en cuatro grupos: Control (solución salina) y alta; 0,3 mg/kg, medio; 0,03 mg/kg, bajo; 0,003 mg/kg de letrozol. Se administró solución salina y letrozol en soluciones de 100 mL por vía intraperitoneal desde el día 11 hasta el día 15 de la preñez. El desarrollo del sistema esquelético de los fetos se examinó con tinción esquelética doble, métodos de tinción inmunohistoquímica y microscopía electrónica de barrido de densidad mineral. Se incluyeron en el estudio un total de 100 fetos de ratas hembra, 25 en cada grupo. Como resultado, se observó que las tasas de osificación disminuían dependiendo de la dosis de letrozol en los huesos de los miembros torácicos (escápula, húmero, radio, ulna) y de las miembros pélvicos (fémur, tibia, fíbula). Se encontró una disminución estadísticamente significativa en las tasas de osificación de todos los huesos entre el grupo control y los grupos de letrozol bajo, medio y alto (p<0,001). La exposición a letrozol durante la preñez afectó negativamente la osificación y el crecimiento óseo. Sin embargo, los efectos teratogénicos del letrozol no están claros por lo que debe ser investigado más extensamente.

Efeitos do citrato de clomifeno, letrozol e estradiol sobre apoptose em células do cumulus oophorus humano / Effects of clomiphene citrate, letrozole and estradiol on apoptosis in human cumulus oophorus cells

Citrato de clomifeno (CC) e letrozol (LE) são indutores de ovulação que, apesar das altas taxas de ovulação confirmada, atingem baixas taxas de gravidez. Este estudo teve como objetivo investigar os efeitos de CC e LE in vitro, isoladamente ou em combinação com estradiol (E), na apoptose de células do cumulus oophorus humano. Realizamos um estudo prospectivo controlado utilizando culturas primárias de células do cumulus de pacientes submetidas à fertilização in vitro (n=22). A coloração com Giemsa e a imunocitoquímica para alfa-inibina foram utilizadas para avaliar a pureza e a morfologia da cultura celular. A viabilidade celular foi avaliada pelo ensaio MTT, o ciclo celular por citometria de fluxo e a expressão gênica de Caspase-3, Bax e Superóxido dismutase 2 (SOD-2) e S26 por reação em cadeia de polimerase (PCR) em tempo real. As células foram tratadas por 24 horas em 5 grupos de tratamento: CC, CC + E, LE, LE + E e controle. Nenhum dos tratamentos afetou a viabilidade celular, mas o LE reduziu a porcentagem média de células na fase S em relação ao controle (24,79 versus 21,70, p=0,0014). O tratamento com CC aumentou a expressão gênica de Bax (4 vezes) e SOD-2 (2 vezes), que foi revertida quando adicionado E à cultura. A expressão de SOD-2 aumentou em células tratadas com LE quando comparado ao controle (4 vezes), que foi também revertida por adição de E. Estes achados sugerem que CC e LE não afetam significativamente a viabilidade das células do cumulus humana. Porém, houve modulação na expressão de genes envolvidos na apoptose por essas drogas isoladamente e em associação com E, sugerindo que CC e LE podem ter efeitos diretos nas células do cumulus além de seus mecanismos de ação conhecidos.

Clomiphene citrate (CC) and letrozole (LE) are ovulatory stimulants that, despite high ovulation rates, achieve low pregnancy rates. This study aimed to investigate the in vitro effects of CC and LE, alone or in combination with estradiol (E), on apoptosis in human cumulus cells. We performed a controlled prospective study using primary cumulus cell cultures from patients undergoing in vitro fertilization (n=22). Giemsa stain and alpha-inhibin immunocytochemistry was used to assess cell culture purity and morphology. Cell viability was evaluated by MTT assay, cell cycle status by flow cytometry, and Caspase-3, Bax and superoxide dismutase 2 (SOD-2), and S26 gene expression by real-time polymerase chain reaction (qPCR). Cells were treated for 24 hours in 5 conditioned media: CC, CC + E, LE, LE + E and control. None of the treatments affected cell viability, but LE reduced the mean percentage of cells in the S phase compared to control (24.79 versus 21.70, p=0.0014). CC treatment increased mRNA expression of Bax (4 fold) and SOD-2 (2 fold), which was reversed by co-treatment with E. SOD-2 expression increased in cells treated with LE compared to control (4 fold), which was also reversed by E. These findings suggest that CC and LE do not significantly affect the viability of human cumulus cells. Still, the expression of genes involved in apoptosis was modulated by these drugs alone and in association with E, suggesting that CC and LE may have direct effects on cumulus cells beyond their known mechanisms of action.

Atualizações na terapêutica farmacológica para infertilidade na mulher diagnosticada com síndrome de ovários policísticos: revisão de literatura / Updates on pharmacological treatments for infertility in women diagnosed with polycystic ovary syndrome: a literature review

Objetivo: Abordar atualizações referentes à terapia medicamentosa para indução da ovulação nas mulheres diagnosticadas com síndrome dos ovários policísticos (SOP). Métodos: Revisão de literatura por meio de levantamento bibliográfico do período de 1975 a 2021, nas bases eletrônicas PubMed, SciELO e MedLine, complementado pela Diretriz Internacional Baseada em Evidências para a Avaliação e Manejo da SOP de 2018 e pelo manual da Febrasgo para SOP. Sete descritores que atendessem à finalidade da pesquisa foram utilizados. Resultados: A literatura aponta atualmente algumas drogas como opção na terapêutica para a indução de ovulação, como metformina, letrozol e citrato de clomifeno, evidenciando que o uso de letrozol isolado e em associação com a metformina apresentaram melhores taxas de ovulação, 71,5% e 75,4%, respectivamente. Conclusão: O uso do letrozol isolado ou combinado com a metformina apresentou os melhores resultados nas taxas de gravidez e ovulação, todavia o tratamento para indução ovulatória deve ser individualizado.(AU)

Objective: To address updates of medicinal therapy for ovulation induction in women diagnosed with polycystic ovary syndrome (PCOS). Methods: Reviewing Literature through a bibliographic survey from 1975 to 2021, on the electronic databases PubMed, SciELO and MedLine, complemented by the International Evidence-Based Guideline for the Evaluation and Management of PCOS 2018 and the Febrasgo guide for PCOS. Seven descriptors that matched to the purpose of the research were applied. Results: Some drugs are currently indicated in the literature as an option for ovulation induction therapy, such as: metformin, letrozole and clomiphene citrate, showing that the use of letrozole alone and in association with metformin had better ovulation rates, 71.5% and 75.4%, respectively. Conclusion: The use of letrozole alone or combined with metformin showed the best results in pregnancy and ovulation rates, however, treatment for ovulatory induction must be individualized.(AU)

Clomiphene versus letrozole: a better agent for ovulation induction

Background: Anovulatory dysfunction is a commonly encountered problem which is responsible for about 40% of female infertility. One of the leading causes of female infertility is polycystic ovarian syndrome (PCOS). Clomiphene citrate has been the drug of choice in treating women with anovulatory infertility. However, in recent years, letrozole, an aromatase inhibitor, has emerged as alternative ovulation induction agent. Aim of this study was to compare efficacy of clomiphene citrate and letrozole as first line therapy for ovulation induction in polycystic ovarian syndrome.Methods: This study was a hospital based prospective comparative study done in MVJ MC and RH involving 100 females suffering from infertility due to anovulation. They were divided into 2 groups of 50 each. One group was given clomiphene citrate 50 mg while another group was given letrozole 2.5 mg from day 3 to day 7 of menstrual cycle. Ultrasonographic follicular monitoring was done and injection beta HCG 5000 IU was given once follicle reached optimum size (≥18 mm) and endometrial thickness was adequate (≥7 mm). Patients were advised for timed intercourse after 24-36 hours of HCG administration. Ovulation was detected by sonographic findings of follicular rupture done after 48 hours. Primary outcomes measured were number of growing follicles (≥18 mm), endometrial thickness, ovulation rate and pregnancy rate.Results: In our study there was significant difference in the outcomes of ovulation induction between letrozole group and clomiphene group.  Women who received letrozole showed improved endometrial growth (8.44 mm versus 7.86 mm), ovulation rate (72% versus 56%) and pregnancy rate (22.2% versus 14.3%) than those who received clomiphene. However, variation in follicular growth was negligible between the two groups (1.28 versus 1.36).Conclusions: Letrozole is a superior alternative to clomiphene citrate for ovulation induction in cases of PCOS with anovulatory menstrual cycle, and can be considered as first-line therapy for ovulation induction in such women.

Study of hundred cases of infertility in polycystic ovarian syndrome and its management outcome

Background: Polycystic ovarian syndrome (PCOS) is relatively common endocrine disorder in reproductive aged women, which leads to reproductive, metabolic and endocrine abnormality. About 70 to 80% patients with PCOS have complained of infertility due to anovulation. Due to advanced diagnostic facility by endoscopic evaluation in infertility, incidence of PCOS has increased now a days.Methods: This is study of 100 cases of infertility with polycystic ovarian syndrome and its pregnancy outcome. In this study, from May 2019 to April 2020, 100 cases of infertility with PCOS were studied at tertiary care hospital. Hormonal assay, ultrasound and laparoscopy were used as diagnostic technique. Clomiphene citrate, letrozole, metformin, and laparoscopic ovarian drilling were used as treatment modalities.Results: The maximum number of patients in the study group are seen in the age group of 21-25 years. Menstrual irregularities are the most common presenting symptom affecting 70% females. Primary infertility is most commonly associated with PCOS. In PCOS, there is increased LH:FSH ratio. On USG examination, there are enlarged ovaries in 82% cases.Conclusions: PCOS is an emerging disease of new generation with high prevalence in infertile women. After proper diagnosis, management with lifestyle modification, pharmacotherapy with clomiphene citrate, letrozole and metformin are used as per necessities. Operative laparoscopy with ovarian drilling is the main treatment which results in good conception rate.

Changes of tyrosine phosphorylation in liver and kidney of polycystic ovarian rats induced by letrozole / Cambios de fosforilación de tirosina en hígado y riñón de ratas ováricas poliquísticas inducidas por letrozol

Letrozole (Letro) is a drug commonly used for breast cancer treatment since it can decrease estrogen level. In experimental animal, the Letro has been used to induce the polycystic ovarian syndrome (PCOS) model. Tyrosine phosphorylation (TyrPho) is an essential process in various biological functions both normal and abnormal conditions especially reproduction. Although some side effects of Letro are reported, the alterations of TyrPho responsible for liver and kidney functions have never been demonstrated. In this study, the blood serum, liver, and kidney of control and PCOS rats induced with Letro (orally, 1 mg/ KgBW) for consecutive 21 days were used to determine the serum biochemical components and to investigate the TyrPho expression using western blot analysis. Histopathology of such tissues was observed by Masson's trichrome staining. The results showed that Letro did not affect histological structures but significantly increased the serum levels of urea nitrogen, cholesterol, triglyceride, HDL, LDL, ALT, AST, and alkaline phosphatase. Additionally, the TyrPho protein expressions of 32 and 27 kDas in liver and of 55 and 43 kDas in kidney were increased while of a kidney 26 kDa was decreased as compared to those of control. In conclusion, this recent study indicated that the changes of TyrPho proteins in liver and kidney induced with Letro associated with their functions by alteration of serum biochemical levels.

El letrozol (Letro) es un medicamento utilizado comúnmente para el tratamiento del cáncer de mama, debido a que puede disminuir el nivel de estrógeno. En animales de experimentación, el Letro se ha utilizado para inducir el modelo de síndrome de ovario poliquístico (PCOS). La fosforilación de tirosina (TyrPho) es un proceso esencial en diversas funciones biológicas, tanto en condiciones normales como anormales, especialmente en la reproducción. A pesar de informes que indican algunos efectos secundarios de Letro, no se han demostrado las alteraciones de TyrPho responsables de las funciones hepáticas y renales. En este estudio, el suero sanguíneo, el hígado y el riñón control y las ratas PCOS inducidas con Letro (por vía oral, 1 mg / KgBW) durante 21 días consecutivos se usaron para determinar los componentes bioquímicos del suero y para investigar la expresión de TyrPho usando análisis de transferencia Western. La histopatología de los tejidos se observó mediante la tinción tricrómica de Masson. Los resultados mostraron que Letro no afectó las estructuras histológicas, pero aumentó significativamente los niveles séricos de urea, colesterol, triglicéridos, HDL, LDL, ALT, AST y fosfatasa alcalina. Además, las expresiones de la proteína TyrPho de 32 y 27 kDas en el hígado y de 55 y 43 kDas en el riñón aumentaron mientras que en un riñón disminuyeron 26 kDa en comparación con el control. En conclusión, este estudio indicó que los cambios de las proteínas TyrPho en el hígado y los riñones inducidos con Letro se asociaron con sus funciones mediante la alteración de los niveles bioquímicos en suero.

Comparative study of clomiphene citrate versus letrozole as first-line ovulation induction drug in infertile polycystic ovary syndrome women

Background: Polycystic ovary syndrome is the commonest endocrinopathy resulting in anovulatory infertile young women. Clomifene citrate (clomiphene) is a long-standing standard drug for ovulation induction, and is still considered as first line option in PCOS women. However, clomiphene has certain disadvantage letrozole an aromatase inhibitor acts by reducing estrogen production and has no adverse effects on endometrium and cervical mucous. Indian PCOS women have high prevalence of insulin resistance and thus are likely to have high clomiphene resistance. So letrozole could prove to be a good alternative for ovulation induction in such women.Methods: This was a prospective randomized, parallel, comparative clinical trial of two ovulation induction drugs letrozole 5 mg versus clomiphene citrate 100 mg as first-line ovulation induction drug in infertile polycystic ovarian syndrome women. The target population of the study was one hundred infertile women with PCO (taking at least 2 Rotterdam’s parameters). 50 women were allocated to clomifene citrate and 50 were allocated to Letrozole for ovulation induction. Parameters like age, duration of infertility, B MI, ovulation rate, number of follicles, pregnancy rate, endometrial thickness were noted and analyzed.Results: In letrozole group, the ovulation rate, mono-follicular development, mean endometrial thickness and pregnancy rate was better in comparison to clomifene citrate group.Conclusions: The result of this study suggests that letrozole may replace clomiphene as the first line drug for ovulation induction in infertile PCOS women.

Role of endometrial thickness in natural and stimulated cycles in infertility

Background: The endometrium plays an important role in infertility. The growth of endometrium depends on serum oestradiol level and blood flow to the uterus. A thin endometrium is defined as a lining of less than 7 mm which is associated with infertility. The endometrium is best seen on Transvaginal scan (TVS). The purpose of this study was to evaluate the role of endometrial thickness and its outcome in natural and stimulated cycles in infertile women.Methods: This prospective cohort study was conducted from June 2018 to May 2019 in LLRM Medical College Meerut, Uttar Pradesh, India. Total 150 infertile women of age less than 35 years presented with either primary or secondary infertility were enrolled. Each patient was undergoing transvaginal scan (TVS) to measure endometrial thickness follicular monitoring.Results: The endometrial thickness and pregnancy rate was higher in letrozole induced group as compared to clomiphene with estradiol valerate and clomiphene with sildenafil citrate induced group.Conclusions: Letrozole had better effect on endometrial thickness and pregnancy rate as compared to clomiphene citrate with estradiol valerate and clomiphene citrate with sildenafil citrate.

Lomiphene citrate versus letrozole as first line ovulation induction drug in infertile anovulatory polycystic ovarian syndrome women: a prospective randomized controlled trial

Background: The present study was design to compare letrozole (5 mg) and clomiphene citrate (100 mg) as first line ovulation induction drug in infertile anovulatory polycystic ovarian syndrome (PCOS) women.Methods: This prospective randomized clinical trial included 60 cases of PCOS with anovulatory infertility. The first group comprised of 30 patients who received 5 mg letrozole daily and the second group received 100 mg clomiphene citrate daily for 5 days starting on day 2-5 of menses. Both the groups were followed by ultrasound for follicle monitoring, ovulation and endometrial thickness. When dominant follicle reaches a diameter of more than or equal to 18mm and endometrial thickness ≥7.5 mm, human chorionic gonadotrophin (hCG) 5,000 IU was given intramuscularly and timed intercourse was advised. Main outcome measures were occurrence of ovulation, endometrial thickness and pregnancy rates.Results: The mean age, body mass index, and number of cases of primary and secondary infertility in both the groups showed no statistically significant difference. Multi-follicular development during induction was statistically significantly greater in the clomiphene group (1.27±1.11 versus 2.03±1.65; p=0.041). Ovulation occurred in 24 subjects (80%) in letrozole group and 18 subjects (60%) in the clomiphene group, with a statistically significant difference between the two groups (p=0.024). Pregnancy occurred in 16 subjects (53.33%) in letrozole group and 7 subjects (23.33%) in clomiphene group, which shows statistically significant difference between the two groups (p=0.048).Conclusions: Though number of developing follicles was found statistically significant with clomiphene citrate but ovulation rate and pregnancy rate were higher with letrozole group. Therefore, letrozole is a safe and better alternative for ovulation induction in patients of anovulatory PCOS, and it may be considered as a first line treatment for ovulation induction in these patients.

Clomiphene citrate versus letrozole for ovulation induction in anovulatory infertility: a prospective study

Background: The objective of this study was to compare clomiphene citrate with letrozole for ovulation induction in anovulatory infertile women.Methods: This study was conducted in the infertility clinic and department of obstetrics and gynecology, S.P. Medical College and Associated P. B. M. Hospital, Bikaner, Rajasthan, from 1st August 2018 to 31st July 2019. The study group comprised of infertile females attending infertility clinic or gynae outdoor in department of obstetrics and gynecology, S. P. Medical College Bikaner for infertility. 100 women with anovulatory infertility were enrolled in the study after fulfilling the inclusion and exclusion criteria. Proper counseling was done and written informed consent taken.Results: Ovulation rate was statistically significantly greater in letrozole group. Monofollicular development was statistically significant greater in let group (CC 18%, Let 66%). The endometrial thickness on the day of ßhCG administration in CC group was 7.40±1.08 mm and in let group was 8.20±0.82 mm. Letrozole treated cases had better trilaminar pattern of endometrium as compared to clomiphene. The pregnancy rate was higher in letrozole group.Conclusions: As compare to clomiphene, letrozole is associated with higher pregnancy rate and ovulation rates among infertile women with anovulation.

Letrozole versus gonadotropin-releasing hormone antagonist during luteal phase in the prevention of ovarian hyperstimulation syndrome: a randomized controlled trial / 中华妇产科杂志

Objective@#To explore and compare the preventive effect of using letrozole and gonadotropin-releasing hormone (GnRH) antagonist during luteal phase of patients at high risk for ovarian hyperstimulation syndrome (OHSS).@*Methods@#A total of 99 infertile women undergoing in vitro fertilization and embryo transfer or intracytoplasmic sperm injection with high risk for OHSS were enrolled in this randomized controlled trial.The letrozole group (n=51) received letrozole of 7.5 mg daily for 3 days;the GnRH antagonist group (n=48) were given cetrorelix of 0.25 mg subcutaneously daily for 3 days. Both groups received support therapy combined with embryo cryopreservation. The incidence of OHSS was surveyed. And the serum concentration of estradiol, LH and progesterone on days 3, 5 and 8 after oocytes retrieval were measured.@*Results@#There were no statistical differences in terms of baseline characteristics of patients and outcomes of controlled ovarian hyperstimulation between the two groups.The incidence of moderate and severe OHSS was found no significantly difference between letrozole group [11.8%(6/51)] and GnRH antagonist group [10.4%(5/48);P>0.05]. The estradiol concentration of the indicated days on days 3,5 and 8 after oocytes retrieval in letrozole group and GnRH antagonist group were (1 417±3 543) versus (15 210±9 921) pmol/L, (1 692±4 330) versus (18 680±11 567) pmol/L, (239±336) versus (3 582±5 427) pmol/L, respectively;compared with GnRH antagonist group, the estradiol level was significantly lower in the letrozole group (all P<0.01). The luteinizing hormone level in the letrozole group were (0.46±0.40), (0.56±0.55)and (0.67±0.58) U/L on days 3,5 and 8 after oocytes retrieval, which were significantly higher than those of GnRH antagonist group [(0.28±0.28), (0.30±0.19) and (0.45±0.37) U/L, respectively; all P<0.05]. There was no obvious differences on progesterone levels between letrozole group and GnRH antagonist group (all P>0.05),and on days 8 after oocytes retrieval,the level of progesterone in each group were significantly lower than those on day 3 and 5 after oocytes retrieval (P<0.05).@*Conclusion@#Letrozole has the same efficiency as GnRH antagonist for the prevention of OHSS, faster and cheaper to use, but its efficacy seems not to be related to the suppression of steroidogenic during the luteal phase.

Comparative evaluation of different cost effective ovulation induction drugs and their effect on follicular growth, endometrial thickness and pregnancy outcome

Background: Ovulatory dysfunction is a common cause of female infertility, occurring in up to 20 - 30% of infertile women. The most commonly prescribed ovulation drugs are clomiphene citrate (CC), tamoxifen, aromatase inhibitors (such as letrozole) and gonadotropins. Objective of the study was to evaluate the efficacy of clomiphene citrate, letrozole and tamoxifen for ovulation induction in anovulatory infertility.Methods: Randomized open label interventional clinical trial. Patients were randomized to 3 drug groups. After baseline investigations, they were subjected to ovulation induction and then USG monitoring of follicular growth and ovulation. The primary outcome measured was occurrence of conception. Secondary outcome was effect on endometrial thickness and ovulation rate.Results: In the study, letrozole group showed 100% mono-follicular response. Mid cycle endometrial thickness in about 17% of cases in CC group is ≤8 mm. But all the cases in tamoxifen and letrozole group have ET >8 mm. This difference is statistically significant. The ovulation and conception rates are highest in letrozole group but the difference was not statistically significant.Conclusions: Letrozole produces higher mid cycle endometrial thickness, 100% mono follicular development than clomiphene and tamoxifen. This difference is found to be statistically significant. Ovulation rate and conception rate is highest in letrozole group. But there is no statistically significant difference among the three drugs.

Clomiphene citrate plus N-acetyl cysteine versus letrozole for induction of ovulation in infertile patients with polycystic ovarian disease: a randomized clinical trial

Background: Polycystic ovarian disease (PCOD), a common endocrine disorder with multisystem affection, is the most common cause of anovulatory infertility. Our objective is to evaluate the effect of using clomiphene citrate (CC) plus N-acetyl cysteine (NAC) versus letrozole in ovulation induction in infertile patients with PCOD.Methods: Reproductive-aged infertile women either primary or secondary diagnosed as PCOD according to Rotterdam criteria, 2003 were considered for enrollment. Eligible women for were recruited and randomized (1:1) to receive either CC 100 mg plus NAC 600 mg (CC+NAC arm) or letrozole 5 mg (NCT03241472, clinicaltrials.gov). All medications were started from day 3 of the menstrual cycle for 5 days. The primary outcome was the ovulation rate in both groups. Secondary outcomes included the mid-cyclic endometrial thickness, ovarian hyperstimulation, and clinical pregnancy and miscarriage rates.Results: One hundred ten patients were enrolled and randomized to CC+NAC arm (n=55) or letrozole (n=55). The ovulation rate in patients in letrozole arm was significantly higher than CC+NAC arm (71.8% versus 53.2%, p=0.01). Additionally, endometrial thickness was higher in letrozole arm (mean±SD: 11.46±1.61 versus 9.0±1.13, p=0.031). However, no statistical significant difference with regarding the ovarian hyperstimulation rate (1.8% versus 3.6%, p=0.157), clinical pregnancy rate [3/19 patients (27.3%) versus 19/55 (34.5%), p=0.409] and miscarriage rate [4/15 patients (26.7%) versus 19/55 (15.8%), p=0.317] in CC+NAC versus letrozole groups respectively.Conclusions: Addition of NAC to CC in ovulation induction leads to comparable pregnancy rate as letrozole. However, letrozole produces high ovulation rate and the better mid-cyclic endometrial thickness.

Association of age and body mass index with response to clomiphene citrate or letrozole as treatment for anovulatory infertility in a sample of Filipino women

@#<p style="text-align: justify;"><strong>BACKGROUND:</strong> Clomiphene citrate is used as the first line drug for anovulatory infertility treatment. When a woman fails to ovulate using clomiphene at maximum dose, letrozole is used as a second line drug.</p><p style="text-align: justify;"><strong>OBJECTIVE:</strong> To determine association between a patient's age and body mass index (BMI) and their response to clomiphene citrate or letrozole in the treatment of anovulation-related infertility.</p><p style="text-align: justify;"><strong>MATERIALS AND METHODS:</strong> The authors reviewed 147 patient records from January 2011 to August 2016 and investigated the age, BMI and response of patients when given clomiphene or letrozole for ovulation induction.</p><p style="text-align: justify;"><strong>RESULTS:</strong> Ninety-nine (99) patients received clomiphene citrate while the other 118 patients received letrozole. Those who responded positively to clomiphene were at least 35 years old (72.2%) or had above normal BMI (61.5%). Patients who responded positively to letrozole were at least 35 years old (95%) and were categorized with above normal BMI (82.9%). The authors found that patients who are older than 35 years of age are more likely to respond to letrozole compared to younger patients.</p><p style="text-align: justify;"><strong>CONCLUSION:</strong> This study found no significant association between BMI and response to either Letrozole or Clomiphene. Patients who are more than 35 years old are more likely to respond to letrozole, compared to younger patients. </p>

Clinical analysis of the recombinant human growth hormone combined with letrozole in the treatment of short pubertal boys / 中国实用儿科杂志

OBJECTIVE: To explore the therapeutic effects and adverse reactions of a combination treatment of recombinant human growth hormone(rh GH)with letrozole,compared with rh GH alone,in short pubertal boys. METHODS: Fifty-five short pubertal boys were divided into two groups,one group was treated with rh GH(rh GH group,n=24),and the other group was treated with the combination of rh GH and letrozole(combination group,n=31). All boys had completed the over one year of treatment. The advancement of bone age(BA),height standard deviation score by bone age(Ht SDSBA),body mass index standard deviation(BMI SDS),glucose and lipid metabolism,and the changes of the external genitalia and adverse reactions were evaluated. RESULTS: The age of two groups was(12.72±0.99)years and(12.90±1.36)years,respectively(P>0.05).The treatment periods were(1.71±0.55)years and(1.58±0.46)years,respectively(P>0.05).Their BA increased(0.96±0.27)years/year and(0.50±0.20)years/year during treatment,respectively(P0.05)respectively during treatment. There were no statistically significant difference in BMI SDS,glucose or lipid metabolism between the two groups.Three boys in combination group suffered from fractures during the treatment. Ultrasound bone density scan showed serious shortage of bone mineral density;after supplemental calcium and calcitriol,bone density increased within 3 to 6 months,and there was no recurrence of fracture. CONCLUSION: Combination of rh GH and letrozole in short pubertal boys could inhibit BA progression and ameliorate HtSDSBA,without affecting the normal sexual development,but bone density may be affected,and long-term follow-up is needed.

Regulation of estrous cycle by Cynodon dactylon in letrozole induced polycystic ovarian syndrome in Wistars albino rats / 대한해부학회지

Pharmacokinetic Study of Letrozole Polymorphs in Rats / 医药导报

Objective To study the gastrointestinal absorption process of three letrozole polymorphs in rats, and evaluate the different pharmacokinetics parameters of different polymorphs. Methods A total of 18 SD rats were given the different letrozole polymorphs. Then the high-performance liquid chromatographic method was used for the determination of plasma concentration of letrozole in these SD rats.Finally the pharmacokinetic parameters among the different polymorphs were calculated. Results Cmax of letrozole crystal form I, crystal form II and crystal form III were (9.247± 4.612) ,(23.387± 9.049) and (15.682±1.589) mg·L-1, respectively, and AUC0→t were(198.115±47.014) ,(476.641±125.467) and (271.817±41.068) mg·L-1·h,respectively. Conclusion The different crystal forms of letrozole result in different plasma concentration in SD rats. Crystal form II may be its preponderant polymorphs which deserves further research and development.